Publications by authors named "B Anne Eberhard"

33 Publications

Performance and psychometric properties of lupus impact tracker in assessing patient-reported outcomes in pediatric lupus: Report from a pilot study.

Lupus 2020 Nov 24;29(13):1781-1789. Epub 2020 Aug 24.

Department of Pediatric Rheumatology, Cohen Children's Medical Center, Lake Success, NY, USA.

Objective: To evaluate the reliability, validity, feasibility and psychometric performance of the Lupus Impact Tracker (LIT) as a patient reported outcome (PRO) measure tool in pediatric systemic lupus erythematosus (pSLE).

Methods: This is a prospective, observational, pilot study where patients aged between 12 and 25 years, fulfilling the 1997 ACR classification criteria for SLE, were enrolled. Over 3 consecutive, routine, clinical visits, the patients completed the LIT alongside the Patient-Reported Outcomes Measurement Information System-Short Forms (PROMIS-SFs), Childhood Health Assessment Questionnaire (CHAQ). Rheumatologists completed the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC-ACR) Damage Index. Demographic, clinical and laboratory data were also collected.

Results: Of 46 patients enrolled, 38 patients completed 2 visits and 31 completed all 3 visits. Seventy-eight percent were female, 33% African American, 28% Asian, 15% Caucasian and 17% Hispanic. The mean (SD) age was 17.2 (2.7) years, with a mean (SD) disease duration of 4.6 (3.1) years. The mean (SD) SLEDAI-2K at enrollment was 3.54 (2.96). In the 38 patients who completed two or more visits, intra-class correlation coefficient and Cronbach alpha were calculated to be 0.70 and 0.91 respectively, signifying good reliability of LIT. The LIT showed positive correlation with CHAQ-Disability Index and majority of the PROMIS-SFs parameters. Construct validity was established against clinical disease activity (SLEDAI-2K).

Conclusion: The preliminary results indicate that the LIT is a reliable and valid instrument to capture PRO in p-SLE. Prospective validation with a larger, multicenter cohort is the next step.
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http://dx.doi.org/10.1177/0961203320951264DOI Listing
November 2020

Pilot Study of the Juvenile Dermatomyositis Consensus Treatment Plans: A CARRA Registry Study.

J Rheumatol 2021 Jan 1;48(1):114-122. Epub 2020 Apr 1.

D.M. Wahezi, MD, Msc, Division of Pediatric Rheumatology, the Children's Hospital at Montefiore, Bronx, New York, USA.

Objectives: To determine the feasibility of comparing the Childhood Arthritis and Rheumatology ResearchAlliance (CARRA) consensus treatment plans (CTP) in treating moderate new-onset juvenile dermatomyositis (JDM) using the CARRA registry, and to establish appropriate analytic methods to control for confounding by indication and missing data.

Methods: A pilot cohort of 39 patients with JDM from the CARRA registry was studied. Patients were assigned by the treating physician, considering patient/family preferences, to 1 of 3 CTP: methotrexate (MTX) and prednisone (MP); intravenous (IV) methylprednisolone, MTX, and prednisone (MMP); or IV methylprednisolone, MTX, prednisone, and IV immunoglobulin (MMPI). The primary outcome was the proportion of patients achieving moderate improvement at 6 months under each CTP. Statistical methods including multiple imputation and inverse probability of treatment weighting were used to handle missing data and confounding by indication.

Results: Patients received MP (n = 13), MMP (n = 18) and MMPI (n = 8). Patients in all CTP had significant improvement in disease activity. Of the 36 patients who remained in our pilot study at 6 months, 16 (44%) of them successfully achieved moderate improvement at 6 months (6/13, 46% for MP; 7/15, 47% for MMP; 3/8, 38% for MMPI). After correcting for confounding, there were no statistically significant pairwise differences between the CTP ( = 0.328-0.88).

Conclusion: We gained valuable experience and insight from our pilot study that can be used to guide the design and analysis of comparative effectiveness studies using the CARRA registry CTP approach. Our analytical methods can be adopted for future comparative effectiveness studies and applied to other rare disease observational studies.
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http://dx.doi.org/10.3899/jrheum.190494DOI Listing
January 2021

Validation of the 2019 European League Against Rheumatism/American College of Rheumatology Criteria Compared to the 1997 American College of Rheumatology Criteria and the 2012 Systemic Lupus International Collaborating Clinics Criteria in Pediatric Systemic Lupus Erythematosus.

Arthritis Care Res (Hoboken) 2020 11;72(11):1597-1601

Steven and Alexandra Cohen Children's Medical Center of New York, Lake Success, New York, and Hofstra Northwell School of Medicine, Hempstead, New York, United States.

Objective: Different classification criteria for systemic lupus erythematosus (SLE) have been proposed for many years. The most widely used and accepted criteria has been the 1997 American College of Rheumatology (ACR) criteria. In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) criteria were published in an attempt to improve the clinical relevance of SLE criteria. In 2017, weighted criteria were proposed that included entry criteria, something the 1997 ACR and the 2012 SLICC criteria did not identify. The aim of the present study was to validate the 2017 weighted criteria, the 1997 ACR criteria, and the 2012 SLICC criteria and compare the sensitivities and specificities in pediatric SLE.

Methods: For the past 15 years, retrospective chart review of patients diagnosed with SLE before age 19 years was conducted. The controls were patients referred for serologies positive for antinuclear antibodies but did not fulfill criteria for diagnosis of SLE at the initial visit or were diagnosed with another autoimmune disease. The 3 classification criteria sets were applied to these patients and compared against a gold standard of physician diagnosis.

Results: A total of 156 patients were diagnosed with SLE. The sensitivity for the 2017 weighted criteria was 0.974 (95% confidence interval [95% CI] 0.936-0.993) and the specificity was 0.984 (95% CI 0.966-0.994). The sensitivity for the 1997 ACR criteria was 0.872 (95% CI 0.809-0.920) and the specificity was 1.00 (95% CI 0.990-1.000). The sensitivity for the 2012 SLICC criteria was 0.974 (95% CI 0.936-0.993) and the specificity was 0.997 (95% CI 0.985-1.000).

Conclusion: The 2017 weighted criteria and the 2012 SLICC criteria were more sensitive than the 1997 ACR criteria. There were no significant differences in sensitivity and specificity between the 2012 SLICC and the 2017 weighted criteria.
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http://dx.doi.org/10.1002/acr.24057DOI Listing
November 2020

Pilot study comparing the childhood arthritis and rheumatology research alliance consensus treatment plans for induction therapy of juvenile proliferative lupus nephritis.

Pediatr Rheumatol Online J 2018 Oct 22;16(1):65. Epub 2018 Oct 22.

University of California, San Francisco, 550 16th Street, 5th Floor, San Francisco, CA, 94158, USA.

Background: To reduce treatment variability and facilitate comparative effectiveness studies, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) including one for juvenile proliferative lupus nephritis (LN). Induction immunosuppression CTPs outline treatment with either monthly intravenous (IV) cyclophosphamide (CYC) or mycophenolate mofetil (MMF) in conjunction with one of three corticosteroid (steroid) CTPs: primarily oral, primarily IV or mixed oral/IV. The acceptability and in-practice use of these CTPs are unknown. Therefore, the primary aims of the pilot study were to demonstrate feasibility of adhering to the LN CTPs and delineate barriers to implementation in clinical care in the US. Further, we aimed to explore the safety and effectiveness of the treatments for induction therapy.

Methods: Forty-one patients were enrolled from 10 CARRA sites. Patients had new-onset biopsy proven ISN/RPS class III or IV proliferative LN, were starting induction therapy with MMF or IV CYC and high-dose steroids and were followed for up to 24 months. Routine clinical data were collected at each visit. Provider reasons for CTP selection were assessed at baseline. Adherence to the CTPs was evaluated by provider survey and medication logs. Complete and partial renal responses were reported at 6 months.

Results: The majority of patients were female (83%) with a mean age of 14.7 years, SD 2.8. CYC was used more commonly than MMF for patients with ISN/RPS class IV LN (vs. class III), those who had hematuria, and those with adherence concerns. Overall adherence to the immunosuppression induction CTPs was acceptable with a majority of patients receiving the target MMF (86%) or CYC (63%) dose. However, adherence to the steroid CTPs was poor (37%) with large variability in dosing. Renal response endpoints were exploratory and did not show a significant difference between CYC and MMF.

Conclusions: Overall, the immunosuppression CTPs were followed as intended in the majority of patients however, adherence to the steroid CTPs was poor indicating revision is necessary. In addition, our pilot study revealed several sources of treatment selection bias that will need to be addressed in for future comparative effectiveness research.
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http://dx.doi.org/10.1186/s12969-018-0279-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196456PMC
October 2018

Perspectives From Family Caregivers of Persons With Spinal Cord Injury in Hospital Versus Rehabilitation: A Pilot Study.

Rehabil Nurs 2019 Nov/Dec;44(6):311-318

Nursing Science & Care Ltd., Winterthur, Switzerland.

Purpose: The study aims to assess differences in family preferences for involvement in the ongoing care of a hospitalized family member with spinal cord injury based on whether the patient was hospitalized for initial rehabilitation (Group R) or hospitalized to treat secondary complications (Group C).

Design: Explorative cross-sectional design.

Method: Family members rated the importance and experience of involvement on five subscales of the Patient Participation in Rehabilitation Questionnaire. Differences among the importance and experience scores between the groups were tested using the Mann-Whitney U test.

Findings: Group C scored the importance to be involved significantly higher than Group R (M = 3.17 vs. M = 4.04, p =.01). No other significant differences between groups were detected.

Conclusion: Family members of patients hospitalized for secondary complications want greater involvement in care compared to those hospitalized for rehabilitation.

Clinical Relevance: Results indicate the need for tailored interventions using a family-centered approach and ongoing needs assessment.
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http://dx.doi.org/10.1097/RNJ.0000000000000143DOI Listing
April 2020

Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease.

Arthritis Rheumatol 2018 09 25;70(9):1508-1518. Epub 2018 Jul 25.

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Objective: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease.

Methods: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare.

Results: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05).

Conclusion: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.
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http://dx.doi.org/10.1002/art.40509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115300PMC
September 2018

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America.

Pediatr Rheumatol Online J 2017 Jun 13;15(1):50. Epub 2017 Jun 13.

School of Medicine, University of Missouri, Columbia, MO, USA.

Background: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Methods: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting.

Results: One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups.

Conclusions: Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.
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http://dx.doi.org/10.1186/s12969-017-0174-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470177PMC
June 2017

Early Outcomes in Children With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Arthritis Rheumatol 2017 07 9;69(7):1470-1479. Epub 2017 Jun 9.

Kimberly A. Morishita, MD, MHSc, David A. Cabral, MBBS: British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.

Objective: To characterize the early disease course in childhood-onset antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and the 12-month outcomes in children with AAV.

Methods: Eligible subjects were children entered into the Pediatric Vasculitis Initiative study who were diagnosed before their eighteenth birthday as having granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss), or ANCA-positive pauci-immune glomerulonephritis. The primary outcome measure was achievement of disease remission (Pediatric Vasculitis Activity Score [PVAS] of 0) at 12 months with a corticosteroid dosage of <0.2 mg/kg/day. Secondary outcome measures included the rates of inactive disease (PVAS of 0, with any corticosteroid dosage) and rates of improvement at postinduction (4-6 months after diagnosis) and at 12 months, presence of damage at 12 months (measured by a modified Pediatric Vasculitis Damage Index [PVDI]; score 0 = no damage, score 1 = one damage item present), and relapse rates at 12 months.

Results: In total, 105 children with AAV were included in the study. The median age at diagnosis was 13.8 years (interquartile range 10.9-15.8 years). Among the study cohort, 42% of patients achieved remission at 12 months, 49% had inactive disease at postinduction (4-6 months), and 61% had inactive disease at 12 months. The majority of patients improved, even if they did not achieve inactive disease. An improvement in the PVAS score of at least 50% from time of diagnosis to postinduction was seen in 92% of patients. Minor relapses occurred in 12 (24%) of 51 patients after inactive disease had been achieved postinduction. The median PVDI damage score at 12 months was 1 (range 0-6), and 63% of patients had ≥1 PVDI damage item scored as present at 12 months.

Conclusion: This is the largest study to date to assess disease outcomes in pediatric AAV. Although the study showed that a significant proportion of patients did not achieve remission, the majority of patients responded to treatment. Unfortunately, more than one-half of this patient cohort experienced damage to various organ systems early in their disease course.
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http://dx.doi.org/10.1002/art.40112DOI Listing
July 2017

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study.

Arthritis Rheumatol 2016 10;68(10):2514-26

Hospital for Sick Children, Toronto, Ontario, Canada.

Objective: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA).

Methods: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons.

Results: In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil.

Conclusion: Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding.
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http://dx.doi.org/10.1002/art.39729DOI Listing
October 2016

Efficacy of an Interinstitutional Mentoring Program Within Pediatric Rheumatology.

Arthritis Care Res (Hoboken) 2016 05;68(5):645-51

Boston Children's Hospital and Brigham and Women's Hospital, Boston, Massachusetts.

Objective: The small size of many pediatric rheumatology programs translates into limited mentoring options for early career physicians. To address this problem, the American College of Rheumatology (ACR) and the Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed a subspecialty-wide interinstitutional mentoring program, the ACR/CARRA Mentoring Interest Group (AMIGO). We sought to assess the impact of this program on mentoring within pediatric rheumatology.

Methods: In a longitudinal 3-year study, participant ratings from the AMIGO pilot program were compared with those after the program was opened to general enrollment. Access to mentoring as a function of career stage was assessed by surveys of the US and Canadian pediatric rheumatologists in 2011 and 2014, before and after implementation of AMIGO.

Results: Participants in the pilot phase (19 dyads) and the general implementation phase (112 dyads) reported comparable success in establishing mentor contact, suitability of mentor-mentee pairing, and benefit with respect to career development, scholarship, and work-life balance. Community surveys showed that AMIGO participation as mentee was high among fellows (86%) and modest among junior faculty (31%). Implementation correlated with significant gains in breadth of mentorship and in overall satisfaction with mentoring for fellows but not junior faculty.

Conclusion: AMIGO is a career mentoring program that serves most fellows and many junior faculty in pediatric rheumatology across the US and Canada. Program evaluation data confirm that a subspecialty-wide interinstitutional mentoring program is feasible and can translate into concrete improvement in mentoring, measurable at the level of the whole professional community.
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http://dx.doi.org/10.1002/acr.22732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786258PMC
May 2016

Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic Lupus Erythematosus.

Arthritis Care Res (Hoboken) 2016 Feb;68(2):195-202

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Objective: To validate clinical indices of lupus nephritis activity and damage when used in children against the criterion standard of kidney biopsy findings.

Methods: In 83 children requiring kidney biopsy, the Systemic Lupus Erythematosus Disease Activity Index renal domain (SLEDAI-R), British Isles Lupus Assessment Group index renal domain (BILAG-R), Systemic Lupus International Collaborating Clinics (SLICC) renal activity score (SLICC-RAS), and SLICC Damage Index renal domain (SDI-R) were measured. Fixed effects and logistic models were calculated to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low-to-moderate versus high lupus nephritis activity (National Institutes of Health [NIH] activity index [AI]) score: ≤10 versus >10; tubulointerstitial activity index (TIAI) score: ≤5 versus >5; or the absence versus presence of lupus nephritis chronicity (NIH chronicity index) score: 0 versus ≥1.

Results: There were 10, 50, and 23 patients with ISN/RPS class I/II, III/IV, and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with lupus nephritis activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between lupus nephritis activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture lupus nephritis chronicity was 23.5% and 91.7%, respectively. Despite being designed to measure lupus nephritis activity, SLICC-RAS and SLEDAI-R scores significantly differed with lupus nephritis chronicity status.

Conclusion: Current clinical indices of lupus nephritis fail to discriminate ISN/RPS class in children. Despite its shortcomings, the SLEDAI-R appears best for measuring lupus nephritis activity in a clinical setting. The SDI-R is a poor correlate of lupus nephritis chronicity.
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http://dx.doi.org/10.1002/acr.22651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720587PMC
February 2016

Effects of obesity on health-related quality of life in juvenile-onset systemic lupus erythematosus.

Lupus 2015 Feb 21;24(2):191-7. Epub 2014 Oct 21.

Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Objective: This study evaluated the effects of obesity on health-related quality of life (HRQOL) measures in juvenile-onset systemic lupus erythematosus (jSLE).

Methods: Obesity was defined as a body mass index (BMI) ≥ 95 th percentile according to the Sex-specific Center for Disease Control BMI-For-Age Charts and determined in a multicenter cohort of jSLE patients. In this secondary analysis, the domain and summary scores of the Pediatric Quality of Life (PedsQL) Inventory and the Child Health Questionnaire (CHQ) of obese jSLE patients were compared to those of non-obese jSLE patients as well as historical obese and non-obese healthy controls. Mixed-effects modeling was performed to evaluate the relationship between obesity and HRQOL measures.

Results: Among the 202 jSLE patients, 25% (n = 51) were obese. Obesity had a significant negative impact on HRQOL in jSLE, even after adjusting for differences in current corticosteroid use, disease activity, disease damage, gender and race between groups. Obese jSLE patients had lower physical functioning compared to non-obese jSLE patients, and to non-obese and obese healthy controls. Compared to their non-obese counterparts, obese jSLE patients also had worse school functioning, more pain, worse social functioning and emotional functioning. Parents of obese jSLE patients worry more. The CHQ scores for obese jSLE patients were also worse compared to non-obese jSLE patients in several other domains.

Conclusion: Our study demonstrates the detrimental effects of obesity on patient-reported outcomes in jSLE. This supports the importance of weight management for the therapeutic plan of jSLE.
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http://dx.doi.org/10.1177/0961203314555537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305011PMC
February 2015

AMIGO: a novel approach to the mentorship gap in pediatric rheumatology.

J Pediatr 2014 Feb;164(2):226-7.e1-3

Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1016/j.jpeds.2013.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786259PMC
February 2014

Validation of the systemic lupus erythematosus responder index for use in juvenile-onset systemic lupus erythematosus.

Ann Rheum Dis 2014 Feb 23;73(2):401-6. Epub 2013 Jan 23.

Division of Rheumatology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, , Cincinnati, Ohio, USA.

Objectives: This study tested the concurrent validity of the systemic lupus erythematosus responder index (SRI) in assessing improvement in juvenile-onset systemic lupus erythematosus (jSLE).

Methods: The SRI considers changes in the SELENA-SLEDAI, BILAG and a 3-cm visual analogue scale of physician-rated disease activity (PGA) to determine patient improvement. Using prospectively collected data from 760 unique follow-up visit intervals of 274 jSLE patients, we assessed the sensitivity and specificity of the SRI using these external standards: physician-rated improvement (MD-change), patient/parent-rated major improvement of wellbeing (patient-change) and decrease in prescribed systemic corticosteroids (steroid-change). Modifications of the SRI that considered different thresholds for the SELENA-SLEDAI, BILAG and 10-cm PGA were explored and agreement with the American College of Rheumatology/PRINTO provisional criteria for improvement of jSLE (PCI) was examined.

Results: The sensitivity/specificity in capturing major improvement by the MD-change were 78%/76% for the SRI and 83%/78% for the PCI, respectively. There was fair agreement between the SRI and PCI (kappa=0.35, 95% CI 0.02 to 0.73) in capturing major improvement by the MD-change. Select modified versions of the SRI had improved accuracy overall. All improvement criteria tested had lower sensitivity when considering patient-change and steroid-change as external standards compared to MD-change.

Conclusions: The SRI and its modified versions based on meaningful changes in jSLE have high specificity but at most modest sensitivity for capturing jSLE improvement. When used as an endpoint of clinical trials in jSLE, the SRI will provide a conservative estimate regarding the efficacy of the therapeutic agent under investigation.
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http://dx.doi.org/10.1136/annrheumdis-2012-202376DOI Listing
February 2014

Inactive disease and remission in childhood-onset systemic lupus erythematosus.

Arthritis Care Res (Hoboken) 2012 May;64(5):683-93

Cincinnati Children's Hospital Medical Center, University of Cincinnati, William S. Rowe Division of Rheumatology, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.

Objective: To define inactive disease (ID) and clinical remission (CR) and to delineate variables that can be used to measure ID/CR in childhood-onset systemic lupus erythematosus (cSLE).

Methods: Delphi questionnaires were sent to an international group of pediatric rheumatologists. Respondents provided information about variables to be used in future algorithms to measure ID/CR. The usefulness of these variables was assessed in 35 children with ID and 31 children with minimally active lupus (MAL).

Results: While ID reflects cSLE status at a specific point in time, CR requires the presence of ID for >6 months and considers treatment. There was consensus that patients in ID/CR can have <2 mild nonlimiting symptoms (i.e., fatigue, arthralgia, headaches, or myalgia) but not Raynaud's phenomenon, chest pain, or objective physical signs of cSLE; antinuclear antibody positivity and erythrocyte sedimentation rate elevation can be present. Complete blood count, renal function testing, and complement C3 all must be within the normal range. Based on consensus, only damage-related laboratory or clinical findings of cSLE are permissible with ID. The above parameters were suitable to differentiate children with ID/CR from those with MAL (area under the receiver operating characteristic curve >0.85). Disease activity scores with or without the physician global assessment of disease activity and patient symptoms were well suited to differentiate children with ID from those with MAL.

Conclusion: Consensus has been reached on common definitions of ID/CR with cSLE and relevant patient characteristics with ID/CR. Further studies must assess the usefulness of the data-driven candidate criteria for ID in cSLE.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336032PMC
http://dx.doi.org/10.1002/acr.21612DOI Listing
May 2012

Consensus treatment plans for induction therapy of newly diagnosed proliferative lupus nephritis in juvenile systemic lupus erythematosus.

Arthritis Care Res (Hoboken) 2012 Mar;64(3):375-83

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Objective: To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE).

Methods: A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance after considering the existing medical evidence and current treatment approaches.

Results: After an initial Delphi survey (response rate = 70%), a 2-day consensus conference, and 2 followup Delphi surveys (response rates = 63-79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypical patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized dosages for 6 months. Additionally, the CTPs describe 3 options for standardized use of glucocorticoids, including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs.

Conclusion: CTPs for induction therapy of proliferative LN in juvenile SLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in juvenile SLE.
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http://dx.doi.org/10.1002/acr.21558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457803PMC
March 2012

A dose schedule for intraarticular steroids in juvenile arthritis.

J Rheumatol 2012 Feb 1;39(2):374-6. Epub 2011 Dec 1.

Steven and Alexandra Cohen Children’s Medical Center of New York, New Hyde Park, New York, USA.

Objective: To determine whether the intraarticular (IA) dose of triamcinolone hexacetonide (TH) or triamcinolone acetonide (TA) influences time to relapse among patients with juvenile idiopathic arthritis (JIA).

Methods: The primary endpoint variable was the time to relapse of arthritis in the affected joint after an intraarticular (IA) injection. A relapse was defined as the reoccurrence of active arthritis in the injected joint. Analysis was carried out including only the first IA joint injection for each patient. Further analysis was conducted including the first knee injection alone. A separate analysis within the IA corticosteroid groups was performed using the Spearman rank coefficient, to determine if dose of IA steroid affected time to relapse.

Results: Records from 186 patients with JIA (145 females, 41 males) injected with either TH or TA were collected from January 1995 through December 2003. All subjects were followed for a minimum of 15 months from the time of IA injection. Of the 794 joint injections, 422 (53.1%) were injected with TH and 372 (46.9%) with TA. There were 111 first joint injections (all joints) with TH and 70 with TA. There were 89 first joint injections (knee only) with TH and 56 with TA. TH proved more effective than TA with respect to the time to relapse for first injection into all joints (10.47 ± 0.42 mo vs 8.66 ± 0.59 mo; p < 0.001), and for first injections into knee only (11.04 ± 0.44 vs 8.99 ± 0.65 mo; p < 0.001). IA doses ranged from 0.4 to 4 mg/kg (mean 1.56 ± 0.76) for TH and from 0.5 to 8 mg/kg (mean 2.54 ± 1.74) for TA. There was no correlation between time to relapse and dose of either TH and TA (r = 0.1, p > 0.5). There was no correlation between time to relapse and sex, duration of illness, age of patient, concurrent medications, or subtype of JIA.

Conclusion: In a larger dataset (794 injections) we have confirmed our previous findings (227 injections) that TH is a more effective IA corticosteroid than TA. In this much larger data analysis, dose of IA corticosteroid in the range we studied did not significantly influence the duration of response.
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http://dx.doi.org/10.3899/jrheum.110125DOI Listing
February 2012

Preliminary criteria for global flares in childhood-onset systemic lupus erythematosus.

Arthritis Care Res (Hoboken) 2011 Sep;63(9):1213-23

Cincinnati Children's Hospital Medical Center, Ohio, USA.

Objective: To develop widely acceptable preliminary criteria of global flare for childhood-onset systemic lupus erythematosus (cSLE).

Methods: Pediatric rheumatologists (n = 138) rated a total of 358 unique patient profiles with information about the cSLE flare descriptors from 2 consecutive visits: patient global assessment of well-being, physician global assessment of disease activity (MD-global), health-related quality of life, anti-double-stranded DNA antibodies, disease activity index scores, protein:creatinine (P:C) ratio, complement levels, and erythrocyte sedimentation rate (ESR). Based on 2,996 rater responses about the course of cSLE (baseline versus followup), the accuracy (sensitivity, specificity, and area under the receiver operating characteristic curve) of candidate flare criteria was assessed. An international consensus conference was held to rank these candidate flare criteria as per the American College of Rheumatology recommendations for the development and validation of criteria sets.

Results: The highest-ranked candidate criteria considered absolute changes (Δ) of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) or British Isles Lupus Assessment Group (BILAG), MD-global, P:C ratio, and ESR; flare scores can be calculated (0.5 × ΔSLEDAI + 0.45 × ΔP:C ratio + 0.5 × ΔMD-global + 0.02 × ΔESR), where values of ≥1.04 are reflective of a flare. Similarly, BILAG-based flare scores (0.4 × ΔBILAG + 0.65 × ΔP:C ratio + 0.5 × ΔMD-global + 0.02 × ΔESR) of ≥1.15 were diagnostic of a flare. Flare scores increased with flare severity.

Conclusion: Consensus has been reached on preliminary criteria for global flares in cSLE. Further validation studies are needed to confirm the usefulness of the cSLE flare criteria in research and for clinical care.
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http://dx.doi.org/10.1002/acr.20507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167979PMC
September 2011

Flares in pediatric systemic lupus erythematosus.

J Rheumatol 2007 Jun 1;34(6):1341-4. Epub 2007 May 1.

Schneider Children's Hospital, North Shore-Long Island Jewish Health System, Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.

Objective: To determine the flare rate and the change in Safety of Estrogens in Lupus Erythematosus: National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA SLEDAI) score with disease flare in pediatric systemic lupus erythematosus (pSLE).

Methods: A retrospective chart review of 62 patients with pSLE (ages 5-20 yrs). A flare was defined as the start of, or increase in, the dose of corticosteroids and/or the addition of an immunosuppressive medication. All pre-flare, flare, and post-flare visits were recorded with a SELENA SLEDAI score calculated for each visit. The flare rate was calculated by dividing the total number of flares in the cohort by the total followup years.

Results: Sixty-two patients were eligible. Forty-seven patients had 112 flares. The average number of flares/patient was 1.8 +/- 2.0 and the mean inter-flare time was 15.4 +/- 17.9 months. The flare rate in pSLE was 0.46 flares/patient-year of followup. The median time to first flare from the date of diagnosis was 14.3 months. Patients with cytopenia, pleuritis, or pericarditis, or a positive antibody to Smith nuclear antigen at the time of diagnosis had a significantly higher flare rate than those who did not. The average SELENA SLEDAI score at presentation was 12.5 +/- 5.4, at the pre-flare visit 6.3 +/- 3.5, and during a flare 7.9 +/- 5.1.

Conclusion: This is the first large study to report a flare rate (0.46 flares/patient-year of followup) in pSLE. The flare rate was similar to what has been reported in pSLE previously but significantly lower than that reported in adults with lupus. The average change in the SELENA SLEDAI score with disease flare is 2 points.
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June 2007

Response of systemic onset juvenile rheumatoid arthritis to etanercept: is the glass half full or half empty?

J Rheumatol 2005 May;32(5):763-5

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May 2005

Comparison of the intraarticular effectiveness of triamcinolone hexacetonide and triamcinolone acetonide in treatment of juvenile rheumatoid arthritis.

J Rheumatol 2004 Dec;31(12):2507-12

Division of Rheumatology, Schneider Children's Hospital, 269-01 76th Avenue, New Hyde Park, NY 11040, USA.

Objective: To compare patients with juvenile rheumatoid arthritis (JRA) injected with triamcinolone hexacetonide (TH) or triamcinolone acetonide (TA) with respect to time to relapse.

Methods: This was a retrospective chart review of 85 patients: 51 patients with JRA who had received a joint injection with TH during the period June 2000-April 2001 and 48 patients who had received a joint injection with TA during the period May 2001-March 2002 who were followed for a minimum of 15 months, after an intraarticular steroid injection.

Results: The primary endpoint variable for the study was the time to relapse of the arthritis in the affected joint following an intraarticular injection. A total of 227 joints were injected, 114 with TH and 113 with TA. In the TH group the mean time to relapse (+/- SE) was 10.14 +/- 0.49 months compared to the TA group at 7.75 +/- 0.49 months (p < 0.0001) using the log-rank test. A proportional hazards (Cox) regression analysis revealed no statistical association between sex, duration of illness, or type of arthritis and relapse time. An analysis was performed on the first intraarticular injection for each patient, with the average time to relapse for all joints injected of 10.36 +/- 0.72 months for TH compared to 8.45 +/- 0.78 months for TA (p < 0.02). A further analysis of the first knee injections showed a relapse time in the TH group of 11.11 +/- 0.81 months compared to 7.95 +/- 0.95 months for TA (p < 0.008).

Conclusion: TH offers an advantage to TA, as there is a longer duration of action leading to an improved prolonged response rate in weight-bearing joints, particularly the knees. The results suggest that TH should be the intraarticular steroid of choice, particularly for the knee joint, in patients with JRA.
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December 2004

Infliximab as a novel therapy for refractory Kawasaki disease.

J Rheumatol 2004 Apr;31(4):808-10

Division of Pediatric Cardiology, Department of Pediatrics, Schneider Children's Hospital, North Shore-Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.

Kawasaki disease (KD) is a multisystem vasculitis of unknown etiology, with coronary artery aneurysms occurring in 25% of untreated cases. With conventional treatment of intravenous immunoglobulin (i.v.IG) and high dose aspirin (ASA) only 4% of patients develop coronary artery aneurysms. Children who are unresponsive present a challenge. Tumor necrosis factor-alpha levels peak during the acute and subacute phase of KD, especially in children who develop coronary artery aneurysms. We describe a 3-year-old male with KD and giant coronary artery aneurysms, unresponsive to multiple doses of i.v.IG and methylprednisolone, who was treated with infliximab. After the first dose he defervesced and his laboratory measures improved.
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April 2004

Panniculitis and lipodystrophy.

Curr Opin Rheumatol 2002 Sep;14(5):566-70

Schneider Children's Hospital, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.

Panniculitis and lipodystrophy are rare disorders of subcutaneous tissue. Recently the incidence of lipodystrophy has been increasing secondary to its appearance in patients with HIV. In this population, the lipodystrophy appears to be a direct consequence of drug therapy. A review of the available literature regarding pathogenesis and treatment options is discussed. The diagnosis of panniculitis has been hampered by problems. The recent literature has concentrated on ways of improving pathologic diagnostic yields, and new aids in diagnosis are presented.
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http://dx.doi.org/10.1097/00002281-200209000-00015DOI Listing
September 2002

Coexistent sickle cell disease and juvenile rheumatoid arthritis: 2 cases with delayed diagnosis and severe destructive arthropathy.

Authors:
B Anne Eberhard

J Rheumatol 2002 Aug;29(8):1802; author reply 1802-3

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August 2002

Psoriatic eruption in Kawasaki disease.

J Pediatr 2000 Oct;137(4):578-80

Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

We describe 10 patients who developed a psoriatic skin eruption during either the acute or convalescent phase of Kawasaki disease. The skin eruption was pustular in 3 patients, but more typical psoriasiform skin lesions were seen in the remaining 7 patients. No patient has yet developed chronic psoriasis.
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http://dx.doi.org/10.1067/mpd.2000.107840DOI Listing
October 2000

Perinatal parvovirus B19 infections: what are the clinical consequences?

Pediatr Hematol Oncol 1997 Nov-Dec;14(6):589-92

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http://dx.doi.org/10.3109/08880019709030917DOI Listing
December 1997

Evaluation of the cytokine response in Kawasaki disease.

Pediatr Infect Dis J 1995 Mar;14(3):199-203

Division of Rheumatology, Hospital For Sick Children, Toronto, Canada.

Intracellular cytokines interleukin 6, tumor necrosis factor (TNF) alpha and TNF-beta were studied in peripheral blood mononuclear cells of patients with Kawasaki disease during the acute, subacute and convalescent stages of the disease utilizing cytokine-specific monoclonal antibodies and indirect immunofluorescence. Intracellular cytokines TNF-alpha and -beta were present only during the acute stage before initiation of therapy and not in the subacute or convalescent phase. Intracellular interleukin 6 was seen in both the acute phase and, in small numbers of patients, in the subacute stage of the illness. Overall 15 of 25 (60%) patients produced at least one intracellular cytokine. In the acute stage both monocyte and lymphocyte cytokines were detected intracellularly, TNF-alpha and TNF-beta in 58% of patients whereas interleukin 6 was seen in only 16%. This study provides evidence to support the involvement of activated mononuclear cells, both T cells and monocytes and their secreted soluble products, cytokines, in the pathogenesis of Kawasaki disease.
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http://dx.doi.org/10.1097/00006454-199503000-00006DOI Listing
March 1995

Perhaps vigintiphobia should only apply to infants with Rhesus erythroblastosis.

J Paediatr Child Health 1994 Aug;30(4):341-4

Department of Paediatrics, Mercy Hospital for Women, Melbourne, Victoria, Australia.

Forty-two children who sustained a serum bilirubin (SBR) level above 339 mumol/L as newborn infants were assessed at our Growth and Development Clinic to determine presence of sequelae. Only one child (2.3%) had mild sensorineural deafness and one child (2.3%) performed below age-matched standards on psychological testing. As the SBR level rose the psychological scores were lower. Three infants had sepsis associated with the hyperbilirubinaemia. Two (maximum SBR levels of 371 and 366 mumol/L) children were normal (General Cognitive Index (GCI) 117 and 119, respectively) and one child (maximum SBR level 556 mumol/L) was borderline abnormal (GCI 74) on psychological testing; he also suffered from Rhesus erythroblastosis. Premature infants recorded a mean GCI of 109.9 (+/- 33.4) and for term infants mean GCI was 110.3 (+/- 17.3; NS); however, the youngest premature infant was 32 weeks' gestation. When maximum SBR level was correlated with GCI and Motor Index (MI) the only significant correlation (r = -0.7445; P = 0.03) occurred in infants with Rhesus erythroblastosis and GCI. Since exchange transfusion has a mortality of between 0.3 and 5.3% and an associated morbidity incidence of 5.2% we suggest that the standard indication for its use (SBR level of 342 mumol/L) should only apply to infants with Rhesus erythroblastosis. The actual SBR level which places a newborn infant at significant risk of bilirubin encephalopathy, where the cause of jaundice is other than Rhesus erythroblastosis, cannot be determined by this study.(ABSTRACT TRUNCATED AT 250 WORDS)
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http://dx.doi.org/10.1111/j.1440-1754.1994.tb00659.xDOI Listing
August 1994

Local synthesis of both macrophage and T cell cytokines by synovial fluid cells from children with juvenile rheumatoid arthritis.

Clin Exp Immunol 1994 May;96(2):260-6

Department of Paediatrics, Hospital for Sick Children, Toronto, Canada.

The production of tumour necrosis factor-alpha (TNF-alpha), TNF-beta and IL-6 in synovial fluid was studied in 50 samples of synovial fluid from 44 children with juvenile rheumatoid arthritis (JRA) by identifying cytokine production at a single-cell level. Post Ficoll-separated synovial fluid mononuclear cells were permeabilized and then intracellular TNF-alpha, TNF-beta and IL-6 protein production was examined using indirect immunofluorescence and murine anti-cytokine MoAbs. All three cytokines were measured in 37 of the 50 samples. In 25 of the 37 samples there was complete concordance; all three cytokines were present in six and absent in 19 samples. At least one cytokine was present in 27/50 (54%) of synovial fluid samples. Overall, TNF-alpha was detected in 22/49 (45%) samples, TNF-beta in 15/41 (37%) and IL-6 in 16/45 (36%) samples. Five patients had serial arthrocentesis, and in these samples there were two patients who had initially positive cytokine production, which on subsequent measurement was negative; in the other three patients there was no change from the previous cytokine production. We provide evidence that synovial fluid mononuclear cells produce monocyte and T cell cytokines in JRA. These findings suggest a role for both T cell and macrophage products in the pathogenesis of JRA, and the potential for modulation of cytokine production as a target for therapeutic intervention.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1534897PMC
http://dx.doi.org/10.1111/j.1365-2249.1994.tb06551.xDOI Listing
May 1994

A comparative study of orthoplast cock-up splints versus ready-made Droitwich work splints in juvenile chronic arthritis.

Disabil Rehabil 1993 Jan-Mar;15(1):41-3

Department of Rheumatology, Hospital for Sick Children, Toronto, Canada.

A comparative study of a purpose-made cock-up orthoplast splint with a ready-made Camp Droitwich splint, was undertaken in 12 children with juvenile chronic arthritis involving the wrists and carpi. The splints were randomly allocated so that in half, the dominant hand received the orthoplast and in half the non-dominant. Assessments of joint range, grip strength and functional activities were undertaken at 3 and 6 months after use of the splint; the durability of the splints was also assessed. Overall both splints performed their function adequately, the Camp Droitwich being preferred for comfort, but the orthoplast maintaining a slightly better joint position.
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http://dx.doi.org/10.3109/09638289309165869DOI Listing
March 1993